The Xiaoxinganling Mountains–Sanjiang Plain region represents a crucial ecological security barrier for the Northeast China Plain and serves as a vital region for national grain production. Over the past two decades, the region has undergone numerous ecological restoration projects. Nevertheless, the combined impact of enhanced vegetation greening and global climate change on the regional hydrological cycle remains inadequately understood. This study employed the distributed hydrological model ESSI-3, reanalysis datasets, and multi-source satellite remote sensing data to quantitatively evaluate the influences of climate change and vegetation dynamics on regional hydrological processes. The study period spans from 2000 to 2020, during which there were significant increases in regional precipitation and leaf area index (p < 0.05). The hydrological simulation results exhibited strong agreement with observed river discharge, evapotranspiration, and terrestrial water storage anomalies, thereby affirming the ESSI-3 model’s reliability in hydrological change assessment. By employing both a constant scenario that solely considered climate change and a dynamic scenario that integrated vegetation dynamics, the findings reveal that: (1) Regionally, climate change driven by increased precipitation significantly augmented runoff fluxes (0.4 mm/year) and water storage components (2.57 mm/year), while evapotranspiration trends downward, attributed primarily to reductions in solar radiation and wind speed; (2) Vegetation greening reversed the decreasing trend in evapotranspiration to an increasing trend, thus exerting a negative impact on runoff and water storage. However, long-term simulations demonstrated that regional runoff fluxes (0.38 mm/year) and water storage components (2.21 mm/year) continue to increase, mainly due to precipitation increments surpassing those of evapotranspiration; (3) Spatially, vegetation greening altered the surface soil moisture content trend in the eastern forested areas from an increase to a decrease. These findings suggested that sub-regional ecological restoration initiatives, such as afforestation, significantly influence the hydrological cycle, especially in areas with higher vegetation greening. Nevertheless, persistent increases in precipitation could effectively mitigate the moisture deficits induced by vegetation greening. The study’s outcomes provide a basis for alleviating concerns regarding potential water consumption risks associated with future ecological restoration and extensive vegetation greening projects, thereby offering scientific guidance for sustainable water resource management.